Epigenetic Basis for Stress Inheritance Demonstrated

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Scientists from the University of Haifa in Israel report that offspring born to stressed rat mothers show stress-induced changes at birth, with altered behavior and gender-related differences that continue into adulthood.

Intergenerational transmission of the stress response has been predominately looked at from the psychological perspective. However, the current study (“Prereproductive Stress to Female Rats Alters Corticotropin Releasing Factor Type 1 Expression in Ova and Behavior and Brain Corticotropin Releasing Factor Type 1 Expression in Offspring”) focuses on the epigenetic regulation of a well-studied contributor to stress response, CRF1, in the intergenerational transmission of patterns of stress response.

The Israeli study is described in a paper in the current issue of Biological Psychiatry.

“We show that chronic unpredictable stress leads to an increase in CRF1 messenger RNA expression in frontal cortex and mature oocytes,” wrote the investigators. “Neonatal offspring of stressed female rats show an increase in brain CRF1 expression. In adulthood, offspring of stressed female rats show sex differences in both CRF1 messenger RNA expression and behavior. Moreover, CRF1 expression patterns in frontal cortex of female offspring depend upon both maternal and individual adverse experience.”

“It seems that CRF1 is a marker molecule that tracks the stress experience across generations, perhaps via the germline, and maternal care is minimally involved in this particular effect,” explained Inna Gaisler-Salomon, research team leader.

They also found behavioral differences between the offspring of stressed and nonstressed females, particularly in tests of emotional and exploratory behavior. Interestingly, CRF1 expression was increased in adult daughters of stressed females, but only if the offspring themselves were exposed to stress. This indicates that in adults, CRF1 expression depends on the mother's stress experiences in combination with the individual's stress experience and their sex.

“So why is this important?” asked Gaisler-Salomon. “Traditionally, it was believed that only genetic information is transferred from generation to generation via eggs and sperm cells. This study contributes to the notion that soft-wired information that is not written into the genetic code can also be transferred from one generation to the next via the germline.”

Many psychiatric illnesses, such as schizophrenia and posttraumatic stress disorder, are related to stress. Better understanding of the related mechanisms can contribute to the development of better diagnostics and improved treatments, added Gaisler-Salomon.